IgG-specific cell-based assay detects potentially pathogenic MuSK-Abs in seronegative MG

Amelia Evoli, Saif Huda, Patrick Waters, Mark Woodhall, Maria Isabel Leite, Leslie Jacobson, Anna De Rosa, Michelangelo Maestri, Roberta Ricciardi, Jeannine M. Heckmann, Angelina Maniaol, Judy Cossins, David Hilton-Jones, Angela Vincent

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective: To increase the detection of MuSK-Abs using a CBA and test their pathogenicity. Methods: Sera from 69 MuSK-RIA-positive patients with myasthenia gravis (MG) (Definite MuSK-MG), 169 patients negative for MuSK-RIA and AChR-RIA (seronegative MG, SNMG), 35 healthy individuals (healthy controls, HCs), and 16 NMDA receptor-Ab-positive (NMDAR-Ab) disease controls were tested for binding to MuSK on a CBA using different secondary antibodies. Results: Initially, in addition to 18% of SNMG sera, 11% of HC and 19% of NMDAR-Ab sera showed positive binding to MuSK-transfected cells; this low specificity was due to anti-IgG (H1L) detection of IgM bound nonspecifically to MuSK. Using an IgG Fc gamma-specific secondary antibody, MuSK-Abs were detected by CBA in 68/69 (99%) of Definite MuSK-MG, 0/35 HCs, 0/16 NMDAR-Ab, and 14/169 (8%) of SNMG sera, providing increased sensitivity with high specificity. The RIA-negative, CBA-positive MuSK-IgG sera, but not IgM-MuSK-binding sera, reduced agrin-induced AChR clustering in C2C12 myotubes, qualitatively similar to RIA-positive MuSK-Abs. Conclusions: An IgG-specific MuSK-CBA can reliably detect IgG MuSK-Abs and increase sensitivity. In the MuSK-CBA, IgG specificity is essential. The positive sera demonstrated pathogenic potential in the in vitro AChR-clustering assay, although less effective than Definite MuSK-MG sera, and the patients had less severe clinical disease. Use of IgG-specific secondary antibodies may improve the results of other antibody tests. Classification of evidence: This study provides Class III evidence that an IgG-specific MuSK-CBA identifies patients with MG.
Original languageEnglish
Pages (from-to)e357-e358
JournalNEUROLOGY® NEUROIMMUNOLOGY & NEUROINFLAMMATION
Volume4
DOIs
Publication statusPublished - 2017

Keywords

  • Neurology
  • Neurology (clinical)

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